title: Susceptibility and mode of binding of the Mycobacterium tuberculosis cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors.
abstract: The cysteinyl transferase mycothiol ligase, or MshC, catalyzes the fourth step in the biosynthesis of the small molecular weight thiol mycothiol. MshC is essential for growth of Mycobacterium tuberculosis. Two groups of known aminoacyl tRNA synthetase inhibitors were evaluated for inhibition of M. tuberculosis MshC including aminoacyl adenosine analogs and natural products. Using enzyme assays, isothermal titration calorimetry and NMR, we show that MshC is selectively inhibited by cysteinyl sulfamoyl adenosine, and that discrimination occurs at the amino acid moiety.
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Gutierrez-Lugo
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bewley
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D008025:Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011485:Protein Binding; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D001688:Biological Products; D008025:Ligases; D000604:Amino Acyl-tRNA Synthetases; D000241:Adenosine